Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
1. Applicant’s election without traverse of Group I (claims 1-19) in the reply filed on June 29, 2026 is acknowledged.
Status of the Application
1. Claims 1-19 are considered for examination. Claim 20 is canceled by the amendment filed on June 29, 2026.
Priority
2. This application filed on December 11, 2024 is a CON of US 18/087,440 filed on December 22, 2022 which is a CON of PCT/US2022/024646 filed on April 13, 2022 which claims priority benefit of US 63/174,789 filed on April 14, 2021.
Claim Rejections - 35 USC § 103
3. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-19 are rejected under 35 U.S.C. 103 as being unpatentable over Daugharthy et al. (WO 2020/028194) in view of Bauer et al. (US 2006/0041385).
Daugharthy et al. teach a method of claim 1, 11, comprising obtaining a tissue sample (para 0103, 00125, 00178, 0004, 0051);
(b) hybridizing a first analyte or first analyte-derived molecule to a capture domain of a capture probe of a plurality of capture probes on an array (para 00115, 00178, 0004-0006, para 0054-0056, 0085, 00103-00108);
(c) extending the capture probe using the analyte as a template, thereby generating an extended capture probe (cDNA) (para 00116, 00178, 0004-0006, 0103-00108);
(d) hybridizing a padlock probe or a snail probe to the extended capture probe (para 0120, 00178, 0007);
(e) circularizing the padlock probe or snail probe (para 00120, 00178, 0007);
(f) amplifying the padlock probe or snail probe, thereby generating an amplified circularized padlock probe or snail probe (para 00121, 00178, 0008);
(g) hybridizing a plurality of detection probes to the amplified circularized padlock or snail probe, wherein a detection probe of the plurality of detection probes comprises: a nucleic acid sequence that is substantially complementary to a sequence of the padlock or snail probe and a detectable probe (para 00178, 00121, 0008); and detecting the signal intensity to determine the localized analyte in the tissue sample (para 00178).
With reference to claims 2-3, 10, 12, Daugharthy et al. that the tissue sample is stained to detect a biomarker to a second analyte (protein) having colocalized expression with the first analyte (para 0103, 00125, 00178, 0051-0054).
With reference to claims 4-5, Daugharthy et al. teach that the padlock or snail probe comprises a first sequence that is substantially complementary to a first portion of the extended capture probe, a backbone sequence and a second sequence that is substantially complementary to a second portion of the extended probe, wherein the first and the second sequences are adjacent sequences (para 0022, 00120, 0054-0055, 00178).
With reference to claims 6, Daugharthy et al. teach that the detectable label is a fluorophore (para 00178).
With reference to claims 7, 9, Daugharthy et al. teach that the method further comprises tissue sample is permeabilized using a permeabilization agent prior to step (b), wherein the agent comprises proteinase K (para 0064, 0067-0070, 0077, 00178).
With reference to claim 8, Daugharthy et al. teach that the tissue sample comprises formalin-fixed paraffin embedded sample, fresh frozen sample or a tissue section (para 0054-0057).
With reference to claim 13, Daugharthy et al. teach contacting a plurality of first probes and second probes to tissue sample on the array, wherein the first and second probes are substantially complementary to a target nucleic acid of the plurality of the target nucleic acids, hybridizing the first and second probes to the target nucleic acid, ligating the first and second probes to generate the ligation product and releasing the ligation product (para 0011, 00125-00126, 0049, 0062).
With reference to claims 14-16, Daugharthy et al. teach that the first and second probes are substantially complementary to adjacent sequence of the target nuclei acid and the first and second probes that hybridize to sequences that are not adjacent to each other on the target nucleic acid are gap filled by DNA polymerase generating extended first probe, wherein the first or second probe is a DNA probe (para 00178, 0049-0050, 00120-0126, 00178).
With reference to claim 17, Daugharthy et al. teach that the releasing the ligation product comprises contacting the tissue sample with an endoribonuclease (RNAse) (para 0078).
With reference to claim 18, Daugharthy et al. teach that the analyte-derived molecule is an analyte capture agent ((para 0054-0055).
With reference to claim 19, Dhagharthy et al. teach that the method further comprises contacting the tissue sample with a plurality of capture agents, wherein the analyte capture agent comprises an analyte binding moiety and an oligonucleotide comprising an analyte binding moiety barcode and an analyte capture sequence that is complementary to the capture domain of the capture probe on the array, and binding moiety to a protein analyte ((para 0054-0057, 0066).
However, Daugharthy et al. did not specifically teach obtaining a first image and a second image.
Bauer et al. teach a method for detecting the location and associating of different targets in a biological sample on a slide, the method comprising staining a polypeptide to produce a first color image and hybridizing a polynucleotide with labeled nucleic acid probes (detection probes) in said tissue sample to detect a signal form the labeled probes in said sample to produce a second color image and comparing the first and second color images (para 0004-0006, 0018-0025, 0043-0049).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the method of Daugharthy et al. with obtaining a first and second image to determine the location of an analyte as taught by Bauer et al. to develop an improved method for detecting the location of an analyte in a biological sample. The ordinary person skilled in the art would have motivated to combine the method of Daugharthy et al. the method as taught by Bauer et al. and
have a reasonable expectation of success that the combination would result in an improved method for identifying the location of the analyte in a biological sample nucleic acids because Bauer et al. explicitly taught that the method provides imaging different target biomarker expression in the same sample that improves the accuracy of detecting target analytes in the sample and associating said targets in the sample (para 0004-0006, 0018) and such a modification of the claims is considered obvious over the cited art.
Double Patenting
4. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
A. Claims 1-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of US patent 12,203,134 (here after the ‘134). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims 1-19 are entirely within the scope of the claims 1-30 of the patent ‘134. Specifically, the method steps in claims 1-19 comprising obtaining a first image of a tissue sample, hybridizing a first analyte to a capture domain of a capture probe of a plurality of capture probes, extending the capture probe, hybridizing a padlock probe or snail probe to the extended capture prob, circularizing, amplifying, hybridizing ta plurality of detection probes to the amplified circularized probe and obtaining a second image of the tissue sample and detecting a signal intensity from the detection probes in the second image are within the scope of the claims 1-30 of the patent ‘134 and are coextensive in scope.
B. Claims 1-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,827,935 (hereafter the ‘935) in view of Bauer et al. (US 2006/0041385). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims 1-19 are entirely within the scope of the claims 1-20 of the patent ‘935. Specifically, the method of the claims 1-19, comprising hybridizing the tissue sample a capture domain of a capture probe of a plurality of capture probes (an array); extending the capture probe using analyte as a template, generating an extended capture probe on the array, hybridizing a padlock probe (splint oligonucleotide) hybridizing a padlock probe or snail probe to the extended capture prob, circularizing, amplifying and detecting sequence in the tissue sample are within the scope of the claims 1-20 of the patent ‘935. However, the claims in the patent ‘935 did not specifically teach obtaining a first image of the tissue sample and detection probes for obtaining a second image.
Bauer et al. teach a method for detecting the location and associating of different targets in a biological sample on a slide, the method comprising staining a polypeptide to produce a first color image and hybridizing a polynucleotide with labeled nucleic acid probes (detection probes) in said tissue sample to detect a signal form the labeled probes in said sample to produce a second color image and comparing the first and second color images (para 0004-0006, 0018-0025, 0043-0049).
It would have been prima facie obvious to one of ordinary person skilled in the art before the effective filing date of the invention to have modify the method of the claims in the patent ‘935 to include obtaining a first image and use of labeled probes to obtain a second image as taught by Bauer et al. to develop an improved method for detecting an analyte in a biological sample. The ordinary person skilled in the art would have been motivated to modify the method of the claims in the patent ‘935 with the method of imaging a biological sample as taught by Bauer et al. and have a reasonable expectation of success because Bauer et al. explicitly taught that the method provides imaging different target biomarker expression in the same sample that improves the accuracy of detecting target analytes in the sample and associating said targets in the sample (para 0004-0006, 0018) and such a modification of the method is considered obvious over the cited prior art.
Conclusion
No claims are allowable.
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Suryaprabha Chunduru
Primary Examiner
Art Unit 1681
/SURYAPRABHA CHUNDURU/Primary Examiner, Art Unit 1681
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